| Project/Area Number |
10670718
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Gifu University |
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Principal Investigator |
SUZUKI Yasuyuki Gifu Univ. Pediatrics Associate Professor, 医学部, 助教授 (00163014)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOZAWA Nobuyuki Gifu Univ. Pediatrics Assistant Professor, 医学部・附属病院, 講師 (00240797)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Adrenoleukodystrophy / Peroxisome / Very long chain fatty acid / Bone marrow transplantation / Membrane protein / 極長錆脂肪酸 / 極長鎖脂肪酸活性化酵素 / ロレンゾ油 |
|---|
| Research Abstract |
Pathophysiology, prevention and treatment of X-linked adrenoleukodystrophy (ALD) were investigated.
1) Natural course of 15 Japanese patients with childhood and adrescent ALD was clarified. Average onset was 8.5 years of age. Though the most common first symptom was visual disturbance (n=7), mental deterioration rapidly progressed. The appearance of bed-ridden and dysphagia were significantly later than that of mental retardation.
2) The effects of BMT in Childhood ALD were described in four Japanese patients. Two elder patients with relatively maintained IQ levels had favorable results. Two younger patients with a rapid course and unmeasurable IQ levels at BMT showed deterioration of neurological functions.
3) The role of PMP70, a peroxisomal membrane protein which has a homology to ALD protein, was investigated. When PMP70 was expressed in CHO cells, the oxidation rate of palmitate was increased, however, the oxidation of lignocerate was decreased. PMP70 is involved in metabolic transport of long chain fatty acids and may form a heterodimer with ALD protein.
4) Genes and functions of several peroxisomal membrane protein were investigated. PEX13 was the pathogenic gene of peroxisomal biogenesis disorders group H. Gene structure and novel 11 mutations of PEX6 were identified in group C peroxisome biogenesis disorders. A point mutation G843D in PEX1 was the temperature-sensitivity causing mutation in group 1 peroxisome biogensis disorder.
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